Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nineteen patients with brain tumors were orally administered 300 mg of UFT (a combination of FT and uracil with a molar ratio being 1:4) before operation and the concentrations of FT, 5-FU and Uracil in tumors and serum were measured by chemical assay. Time course of FT in serum rapidly attenuated, but 5-FU was kept almost constant below 0.014 micrograms/ml. T/B ratio (5-FU in tumor/5-FU in blood) in 11 samples of meningioma was 6.86 +/- 3.67, while in 8 samples obtained from glioblastoma was significantly higher (23.79 +/- 11.43, p less than 0.001). In malignant brain tumors there was a correlation between the concentration of 5-FU and Uracil in tumor (gamma = 0.67). This correlation was more enhanced when the value of Uracil in tumor was over 15 micrograms/g (gamma = 0.81). The concentration of 5-FU in cyst was low, but tended to accumulated later. This result may be based on the diffusion of 5-FU from the surrounding solid part of tumor into the cyst. Our present study demonstrated that enhancing effect of 5-FU in brain tumors, particularly solid malignant glioma, was yielded after oral administration of UFT.
 ...
PMID:[5-FU concentration in brain tumors after co-administration of FT and uracil]. 630 60

Despite extensive characterization of genetic changes in gliomas, the underlying etiology of these tumors remains largely unknown. Spontaneous DNA damage due to hydrolysis, methylation, and oxidation is a frequent event in the brain. Failure of DNA repair following this damage may contribute to tumorigenesis of gliomas. Uracil DNA glycosylase (UDG), an enzyme which excises uracil from DNA, is an important component of the base excision repair pathway. The sequence of a human homologue of uracil DNA glycosylase gene (UNG) has been recently identified. We performed PCR-based SSCP mutational analysis of UNG in 11 sporadic gliomas (six glioblastomas, two anaplastic astrocytomas, and three oligodendrogliomas) and eight glioblastoma cell lines. One out of six sporadic glioblastomas had a point mutation in exon 3, which resulted in a missense mutation in codon 143. None of the eight glioblastoma cell lines or the five non-glioblastoma sporadic gliomas showed a mutation. Genetic alterations of UNG may play a role in the development of a subset of primary glioblastomas.
 ...
PMID:Mutation of the uracil DNA glycosylase gene detected in glioblastoma. 985 92

The error frequency of uracil-initiated base excision repair (BER) DNA synthesis in human and Escherichia coli cell-free extracts was determined by an M13mp2 lacZ alpha DNA-based reversion assay. Heteroduplex M13mp2 DNA was constructed that contained a site-specific uracil target located opposite the first nucleotide position of opal codon 14 in the lacZ alpha gene. Human glioblastoma U251 and colon adenocarcinoma LoVo whole-cell extracts repaired the uracil residue to produce form I DNA that was resistant to subsequent in vitro cleavage by E. coli uracil-DNA glycosylase (Ung) and endonuclease IV, indicating that complete uracil-initiated BER repair had occurred. Characterization of the BER reactions revealed that (1) the majority of uracil-DNA repair was initiated by a uracil-DNA glycosylase-sensitive to Ugi (uracil-DNA glycosylase inhibitor protein), (2) the addition of aphidicolin did not significantly inhibit BER DNA synthesis, and (3) the BER patch size ranged from 1 to 8 nucleotides. The misincorporation frequency of BER DNA synthesis at the target site was 5.2 x 10(-4) in U251 extracts and 5.4 x 10(-4) in LoVo extracts. The most frequent base substitution errors in the U251 and LoVo mutational spectrum were T to G > T to A >> T to C. Uracil-initiated BER DNA synthesis in extracts of E. coli BH156 (ung) BH157 (dug), and BH158 (ung, dug) was also examined. Efficient BER occurred in extracts of the BH157 strain with a misincorporation frequency of 5.6 x 10(-4). A reduced, but detectable level of BER was observed in extracts of E. coli BH156 cells; however, the mutation frequency of BER DNA synthesis was elevated 6.4-fold.
 ...
PMID:Uracil-initiated base excision DNA repair synthesis fidelity in human colon adenocarcinoma LoVo and Escherichia coli cell extracts. 1155 95